Both the brain and the pituitary gland have been known to contain mitogenic factors for cultured cells; however, until 1974, it was unclear what their relationship was with classical pituitary hormones, such as TSH, LH, FSH, GH and ACTH. In 1974, the identification in the pituitary gland of a growth factor called fibroblast growth factor (FGF) was reported which was shown to be distinct from pituitary hormones, Gospodarowicz, D., Nature, 249: 123-127 (1974). This growth factor is now known to have a MW of 16,415, is basic (a pI of 9.6), and is a potent mitogen for either normal diploid fibroblasts or established cell lines. It is thus referred to as "basic FGF" because it exhibits such a basic pI of 9.6 (in contrast to acidic FGF which has an acidic pI of about 5). Purification of an acidic brain FGF is described in U.S. Pat. No. 4,444,760 (Apr. 24, 1984). To distinguish from the acidic FGF, the compounds of present interest are referred to as basic FGF. Later studies confirmed that, in addition to fibroblasts, FGF is also mitogenic for a wide variety of normal diploid mesoderm-derived and neural crest-derived cells, including granulocytes, adrenal cortical cells, chondrocytes, myoblasts, corneal and vascular endothelial cells from either bovine or human origin, vascular smooth muscle cells, and lens epithelial cells. Basic FGF was also shown to substitute for platelet-derived growth factor in its ability to support the proliferation of fibroblasts exposed to plasma-supplemented medium. Consistent with its ability to stimulate the proliferation of bovine vascular endothelial cells, basic FGF has a similar activity in vivo on capillary endothelial cells; therefore, basic FGF is considered an angiogenic factor.
The first above-identified U.S. application, Ser. No. 586,518, the teachings of which are incorporated herein by reference, describes a purification to homogeneity of mammalian basic fibroblast growth factor (FGF) using reverse-phase high performance liquid chromatography (RP-HPLC). The second above-identified U.S. application, Ser. No. 670,160, the teachings of which are incorporated herein by reference, describes a purification to homogeneity of mammalian FGF using heparin-Sepharose affinity chromatography which has certain advantages.